Hampshire, United Kingdom
Prolonged Cryocompression and Skin Temperature: a Safety and Feasibility Pilot
Introduction Despite the advancement in technology for cryocompression therapy in rehabilitation after knee surgery, guide-lines for the duration of cryocompression treatments, remain largely unchanged at typically 15-30 minutes in length (Long and Jutte, 2020). This duration was originally established with the traditional use of ice packs, which provide rapid cooling and must be limited to this relatively short time period to reduce the likelihood of cold-related complications or injury (MacAuley, 2001; Wilke and Weiner, 2003; Thienpont, 2014). Electronic devices have been shown to reduce tissue temperature more gradually, and to provide an effective dose of cold without lowering tissue temperature to potentially unsafe levels (Belsey, Reid, et al., 2024). Consequently, the traditional treatment duration guidelines may not be relevant for electronic devices. Prolonged cooling durations are more likely to effect pain and inflammation around deeper tissues (Long and Jutte, 2020), which could lead to improvements in post-operative clinical outcomes. Exposure to cold of 15 ℃ using a non-electronic technology for up to 6 hours has previously been demonstrated as safe (Kwiecien, McHugh and Howatson, 2020). One study investigated prolonged cooling (3 hours per treatment) with an elec-tronic device following knee surgery and although no complications were reported, skin temperature response was not measured. Therefore, despite safety being indicated, it is not known whether an optimal dose of cooling was applied that reduced skin temperature to within an established optimal therapeutic zone of 10-15 ℃ (Wilke and Weiner, 2003; Bleakley and Hopkins, 2010). The safety and feasibility of prolonged exposure to cryocompression with an electronic device that is known to provide an effective dose of cold has not explicitly been examined, and should be established if traditional treat-ment duration guidelines are to be challenged, amended, and optimised for this therapy modality. Therefore, the aim of this study is to investigate the ability of an electronic cryocompression device to maintain skin tempera-ture within the target therapeutic zone for a prolonged period, and to assess the safety and feasibility of such a treatment protocol. The results from this exploratory pilot study can then be used for future research into the efficacy of prolonged cooling in clinical settings and investigations into optimal treatment duration depending on the therapy modality employed. It is hypothesised that an electronic cryocompression device will successfully reduce skin temperature will be re-duced and maintained within the 10-15 ℃ target range during a prolonged treatment. Secondly, it is predicted that there will be no treatment-related adverse events and the protocol will be well tolerated by participants in terms of perceived comfort. Methods Design This prospective randomised controlled crossover trial will recruit healthy adult volunteers from a university population to participate, in line with previously published recommendations for appropriate sample sizes for pilot studies (Julious, 2005; Johanson and Brooks, 2010). Each participant will take part in each of the two conditions in order to eliminate the risk of demographic factors confounding the results. Conditions will be conducted in a random order, as determined by a random number generator before recruitment begins. Conditions will involve the application of a Physiolab S1 cryocompression device in accordance with the manufacturers' guidelines. Each testing session will take around 3 hours to complete, with at least 24 hours between tests with the same participant. In total, participants will be giving no more than 6 hours of time across 2 days to complete their participation. Participants will not be compensated for taking part in the study, nor will they be charged. Protocol All eligible participants will first be required to provide informed consent prior to their participation in the study, and will be asked to avoid caffeine, tobacco, and strenuous exercise within the 2 hours prior to testing. The height and mass of the participants will be measured at the beginning of the first test session in order to calculate BMI, and participants' age and sex will be recorded to allow for later analysis to determine any confounding influence of these factors on the results. Participants will then be asked to lie supine on a physiotherapy bed for 20-minutes to allow body temperature to acclimatise to the test environment and to ensure that the feet are at the same level as the heart, which is important for the capillary refill test that will be conducted on the second toe of the leg that receives cryotherapy, multiple times throughout the study period. During the 20-minute acclimatisation period, the following anatomical landmarks on the treatment leg will be marked with a small square of micropore tape in preparation for the range-of-motion measurements that will be taken before and after the cryotherapy treatment: greater trochanter, lateral epicondyle, and lateral malleolus. Additionally, the acclimatisation period will also be used to prepare and affix 3 iButton temperature sensors to the treatment leg with more micropore tape: one 20 mm distal to the patella, one in an equivalent position posteriorly, and one on the plantar side of the proximal pulp of the big toe. The two iButtons positioned about the knee have been shown to have the highest reproducibility for human skin temperature measurement around that joint (Priego-Quesada et al., 2021) and will measure changes directly within the cryocompression treatment area. Measurements taken by the iButton on the toe will be used in combination with the results of the capillary refill tests to monitor changes in perfusion as a safety measure during prolonged cryocompression, and to ensure a return to normal following the treatment. The iButton is a small temperature sensor that has been validated for human skin temperature measurement (van Marken Lichtenbelt et al., 2006; Smith et al., 2010). The leg that will be used for the study will be randomly selected for each participant, and will remain the same for each condition. Following the acclimatisation period, a capillary refill test will be conducted on the second toe and skin temperature of the big toe will be measured. A measurement of range-of-motion from extension to flexion will also be taken at this time using a standard goniometer. These measures taken prior to the cryocompression treatment will provide the reference baseline values that will be monitored to ensure the safety of the participant and to detect any abnormal response to the prolonged cooling protocol. Baseline skin temperature measurements around the knee will also be recorded at this point. Once the baseline measures have been taken, the cryocompression device will then be applied to the leg of the participant and the treatment will begin. The first 30 minutes of each test will involve the device being set to circulate cold water at 8 ℃, as this has been shown to reduce skin temperature to within the target 10-15 ℃ range with this device (Belsey, Gregory, et al., 2024). The device will continue to provide a treatment for an additional 90 minutes with water temperature adjusted to either 10 ℃ or 12 ℃, depending on the randomised condition being tested. These temperatures have been chosen to reflect the minimum and maximum temperatures that the device is able to apply that fall within the target skin temperature range. Choosing a water temperature <10 ℃ for prolonged cooling would risk skin temperature dropping to below the target range, as equilibrium may be approached, which could increase the risk of adverse events (Wilke and Weiner, 2003). The device will apply intermittent compression of 25-50 mmHg consistently throughout each test, in line with the manufacturer-recommended setting for knee treatments. Every 30 minutes, the cuff of the device will briefly be removed from the leg of the participant to inspect the skin for any indication of an abnormal reaction. To compliment this visual inspection, a pain rating will be concurrently recorded using a Numerical Pain Rating Scale (NPRS), along with another capillary refill test and skin temperature measurement of the toe. If any adverse events are identified or suspected based on the visual inspection, or if pain scores exceed 5/10 at any time, or if the capillary refill test lasts longer than 6 seconds for two consecutive measurements during the treatment period, the test will be terminated and the participant will take no further part in the study. In addition to the safety checks, a perceived rating of comfort will simultaneously be recorded every 30 minutes by responding to the following question using a 5-point Likert scale: "How would you rate the comfort of the treatment?" The possible answers to this question will be: "Very comfortable, Comfortable, Neutral, Uncomfortable, Very uncomfortable". This will provide insight into differences in tolerance of the treatment, which could be relevant for the feasibility of a prolonged cooling protocol in clinical settings. Following the 2-hour prolonged cooling treatment, the cuff will be removed from the participant and skin temperature will continue to be measured every 5 minutes for a further 15 minutes, as this is the maximum length of time it is expected that skin temperature will remain <15 ℃ while the leg re-warms (Belsey, Gregory, et al., 2024). This will allow for the total time to be measured that skin temperature remains within the target therapeutic range as a result of the cryocompression treatment. At the point of cuff removal and 15 minutes lat-er, capillary refill tests will once again be conducted to monitor the expected normalisation of perfusion of the treatment leg. Normalisation will be defined by capillary refill times are less than 3 seconds in participants under 50 years, and less than 4.5 seconds in participants over 50 years to account for normal age-related differ-ences. 15 minutes after the treatment, a second range-of-motion test will be performed in the same fashion as before to determine whether there is any residual stiffness/weakness as a result of the treatment. Functionally meaningful changes in range-of-motion of the knee have been suggested to be >5 °, so a return to "normal" range-of-motion will be established if the post-test score is within 5 ° of the baseline measure. At this point, a final pain and comfort rating will be recorded and the temperature sensors will be removed from the leg of the participant; thus ending their participation in the test. If the results of the capillary refill test or range-of-motion measurement have not returned to normal as defined above, the treatment leg will be actively re-warmed by being placed in a water bath at 38 ℃ for a further 15 minutes. The capillary refill test and range-of-motion will be measured again at the end of this subsequent 15-minute period. If results have still not returned to within normal parameters, and the participant or researcher has concerns, then medical advice will be sought and attention provided as necessary. Otherwise, the participant will be allowed to leave the lab but will be contacted by the researcher two hours later (by a contact method chosen by the participant) to enquire as to whether there have been any changes. At which point, medical advice can be recommended or sought, if needed. Once each participant has taken part in all conditions, they will have completed their participation in the study . Analysis The data will be analysed to detect any differences during testing compared to baseline measures, and between groups. All data will be first subjected to a Kolmogorov-Smirnov test to assess whether they are normally distributed. A repeated measures analysis of variance will be performed on all normally distributed data. A Friedman test will be performed on any data that are not normally distributed . Ethical issues Although this is a safety study and adverse events will be monitored as outcomes, the risk of any being identified is deemed to be low. Individuals will be screened prior to participation to ensure that nobody who would otherwise be contraindicated for cryocompression therapy is recruited. The temperature settings used during treatments were chosen as they are expected to reduce and maintain skin temperature within the target zone, while preventing it from dropping below the 10 ℃ threshold where the risk of complications is increased. Additionally, a previous study reported no cold-related complications when skin temperature was maintained at 7 ℃ continuously for 2 hours (Morsi, 2002), suggesting that the 10 ℃ threshold is cautious. Similarly, a 2-hour treatment duration has been chosen as a conservative time period for prolonged cooling, as other methods have been safely applied for much longer durations, as outlined in the introduction. Nevertheless, this will be the first time an electronic device providing a known effective dose of cold for a prolonged period of time has been investigated. Therefore, the temperature settings and treatment duration were chosen to keep risk to the participants at an absolute minimum. Participants have the right to withdraw themselves and any collected data from the study at any time during participation, and for 7 days after the final test session, without having to give a reason. They also have the right to terminate a test session at any time. After 7 days have passed since a participant's final test session, their data will be anonymised and used as part of the final dataset for analysis. Testing shall also be terminated as a result of any adverse reactions that emerge. Any adverse reactions that occur shall be addressed and monitored, as appropriate, until things return to baseline/normal. If a test is terminated for a reason that could be mitigated in future, participants will be offered the opportunity to repeat the test another day, should they wish to continue taking part in the study. If a test is terminated due to an adverse reaction that can not be mitigated in future, the participant (and any collected data) will be thanked for their time and withdrawn from the study. All members of the research team have been trained to be able to competently use the cryocompression device and to correctly execute the test protocol outlined above. A qualified first aider will always be present within the labs while tests are being conducted, and all lab rules and safety protocols will be followed at all times (e.g. cleaning up water spills).
Phase
N/ASpan
9 weeksSponsor
University of WinchesterWinchester, Hampshire
Recruiting
Healthy Volunteers
Feasibility of Measuring Vertical Perception in Acute Stroke
The secondary research questions that this study will aim to address are: - What percentage of patients admitted to an acute stroke unit show a positive test for vertical perception loss within four weeks of admission (evidence of subjective visual vertical (SVV) tilt on either bucket test or Catherine Bergego Scale or evidence of subjective postural vertical (SPV) tilt on SCP)? - For those able to complete the assessments, does vertical perception loss show any relationship with: - Discharge (DC) destination - Care package size on discharge - Number of inpatient falls - Level of functional independence on discharge - Is there a trend for any element of the SCP or the Catherine Bergego to be more correlated with SVV tilt. Primary outcomes: The primary outcome is to understand the feasibility of completing the suite of outcome measures in an acute stroke setting. The study will determine the : - Proportion (%) of patients on whom the assessments are attempted. - Percentage of patients who are able to complete all three assessments within four weeks of admission. - Time taken to complete the three measures in an acute clinical setting - A recommendation regarding the most feasible time point to complete these assessments. Secondary outputs: The secondary aims are to gain a further understanding of vertical perception loss in acute stroke patients. - An understanding of factors that prevent or facilitate completion of these three assessments - An understanding of healthcare professionals' experiences of completing these assessments in an acute stroke unit. - An understanding of whether people with stroke (or their advocates) find it appropriate to complete all three assessments in an acute stroke setting. - Percentage of patients admitted to an acute stroke unit showing a positive test for vertical perception loss within four weeks of admission. - To explore the relationship between vertical perception loss and: - Discharge destination - Care package size on discharge - Number of inpatient falls - Level of functional independence on discharge - To explore if any elements of the Catherine Bergego Scale or Scale for Contraversive Pushing show a trend for a relationship to vertical perception loss Trial Setting The population to be studied will be acute stroke patients admitted to a stroke unit. A non-probability, convenience sample will be used. All patients with a diagnosis of stroke admitted for 72 hours to a single stroke unit at Royal Hampshire County Hospital will be considered in the present study. All those admitted to the stroke unit over a six-month period will be eligible for inclusion, meaning approximately 250 people will be screened for participation. Recruitment Potential participants will be identified during the daily handover. Those meeting the inclusion criteria will be approached and invited to participate. This will take place between 48 hours and one week after admission. Potential participants will be provided with the participant information sheet (PIS). If the patient is unable to consent due to cognitive or language impairment or low level of consciousness then their advocate will be approached. Where possible potential participants will be supported to consent using information in different formats (e.g. through use of pictures) or the skill of appropriate members of the clinical team (e.g. speech and language therapists). If a participant who lacked capacity, and was consented by an advocate, regains capacity then their informed consent to continue will be sought. Study protocol For those patients who consent, the qualified physiotherapists or occupational therapists on the stroke unit, will then attempt to complete all 3 outcome measures with the patient. If the patient is unable to complete any elements of the outcome measure for any reason, this will be recorded. If the patient is unable to complete the outcome measures, then an attempt will be made to complete the outcome measures at 1 week post admission, if still unable they will be attempted again at 2 weeks and 4 weeks post admission. At the point participants complete all 3 outcome measures or at 4 weeks (whichever is earliest) most will have no further active participation in the quantitative part of the study. The assessments do not need to all be completed in one sitting and can be spread across sessions. If a patient is unable to be consented at 48 hours they will be consented as soon after this point as possible up to one week after admission, and this will be recorded. If patients are discharged or have a change in status following consenting to participate but prior to completion of the outcome measures any data collected to date will be utilised in the study results and the reasons for non-completion of the outcome measures will be noted as this will inform the feasibility of these outcome measures. The length of time taken to complete the measures will be recorded by the administrator. The expectation is that administration of all three outcome measures will take no longer than one hour. Due to the observational nature of the SCP and Catherine Bergego Scale elements of these can be completed during therapy sessions. At the point the participants are discharged from the stroke unit appropriate information will be extracted from their medical records. At the time of discharge a small sub-selection of the study participants will have the outcome measures reassessed. Participants will be identified as having a mild, moderate or severe vertical perception loss in order to allow a spectrum of loss to be measured during inpatient stay. Once discharged from the stroke unit participants will have no further input into the study. Assessors Outcome measures will be undertaken by a qualified member of the therapy team on the stroke unit. This includes physiotherapists and occupational therapists. All those undertaking the outcome measures will be trained on their use by the main author (AS) to ensure consistency of approach. Additional Research Activities. Focus Groups Prior to the study commencing a focus group will be completed with the therapists undertaking the outcome measures. This will be held following training on the outcome measures. Therapists will be invited to attend by AS at the end of the training session and provided with a PIS. This will allow exploration of how feasible or acceptable the therapists feel it will be to complete the outcome measures before data collection. This can then be compared with their thoughts, and the thoughts of people with stroke and their advocates, on acceptability following use of the outcome measures. At the six month point of the study the focus group will be repeated, with approximately 10 therapists, to allow exploration of the experiences of the therapists that undertook the outcome measures. This will allow collection of data from multiple participants using an unstructured but guided discussion of the use of the outcome measures in the acute stroke setting. Potential participants will be members of the therapy team on the stroke unit who have undertaken the outcome measures.They will be provided with a PIS explaining the post-trial focus groups and the time and date at which the group will be undertaken. They can then decide if they wish to participate or not. If they wish to participate they will be asked to sign a consent form and attend the group at the dedicated time. The groups will be moderated by the lead researcher (AS) using a list of topics/questions to guide the conversation. A second member of the research team, unknown to the participants, will assist in the groups to ensure smooth running of the groups and mitigate for the fact that AS will be known to many participants. Face to face groups will be held in the hospital setting at a time convenient to a majority of participants. The focus groups will last no longer than 1.5 hours. Ground rules will be introduced at the beginning of the groups to allow smooth running of the group and to put participants at ease. Focus groups will be recorded for transcription on MS Teams and stored behind two factor authentication on a password protected computer. Each group member will be assigned a participant number to assist with data analysis. The focus group will be anonymised and transcribed verbatim and following transcription the original recording will be deleted. At this point participants will no longer be able to withdraw from the study. Patient Participant Feedback At the point they complete all the outcome measures (or at 4 weeks if they are unable to complete the measures) participants (or their advocates) will be asked to complete a short survey asking about the acceptability of the outcome measures. Questions will ask about their attitude towards, understanding of and burden of completing the outcome measures. It will be a mix of choice and Likert scale questions with some free text open questions. The survey should take no more than 15 mins to complete. Participants can be supported to complete the survey by an advocate, therapist or member of the research team who can read out the questions and record their responses, but will not influence the answers. The survey will be on paper for ease of completion in the clinical setting. The decision as to whether it is feasible to use these outcome measures to identify those with vertical perception loss will be made on the basis of collated results of this trial.
Phase
N/ASpan
35 weeksSponsor
University of WinchesterWinchester
Recruiting
Robot-Assisted Gait Training in Early-Subacute Stroke
The design of the study This study will be a retrospective-matched non-randomised trial. The physical activity and cardiovascular health of stroke patients using the Lokomat at an inpatient stroke unit (Royal Bournemouth Hospital) will be monitored over time. The same measurements will be conducted with another set of patients at another stroke unit (Royal Hampshire County Hospital) who do not receive any form of RAGT. These patients will be matched retrospectively with those who used the Lokomat at the first study site, and then the results of the two sets of patients will be compared. Both sets of patients will satisfy the inclusion and exclusion criteria. Matching of participants will be based upon baseline Functional Ambulation Category (FAC) score; blood pressure, and age. All members of the research team were involved in the design of this study. Recruitment At the first research site (Royal Bournemouth hospital), when a new patient enters the stroke unit, the care team will assess whether the patients is suitable to receive Lokomat training (as per standard care). If the patient is going to receive Lokomat training, and they satisfy the inclusion criteria of the study (assessed by a member of the clinical care team), a member of the care team will then explain the study to the participant, and provide an information sheet to the patient. They will then have an opportunity to ask any questions they have to either the care team or the research team. If they then decide that they want to participate, then informed written consent will be obtained by a member of the care team. Study participation will not influence which patients are offered or receive RAGT. The patients will not be offered any extra or any fewer sessions if they do or do not decide to participate in the study, and it will be made clear that participation will not influence the care they receive in any way. At the second research site (Royal Hampshire County Hospital) a member of the care team will identify any patient who fits the inclusion criteria. They will then be approached and asked whether they want to hear about the study by a member of the research team. If they do, a member of the research team will explain the study and provide an information sheet. They will then have an opportunity to ask any questions they may have. If they decide that they want to participate in the study, then informed written consent will be obtained by the research team member. Informed consent Potential participants will firstly have a discussion with a member of the research team regarding the study. If they are interested in participating, they will be provided with an information sheet, which will outline the details of the study. The information sheet will include information regarding the purpose of the research, the risks, or burdens to participants (e.g., extra assessments taken, wearing an accelerometer), and details to ensure they know they can withdraw from the study at any time without any consequences. It will also ensure the patient knows participation is entirely voluntary and will not affect their care. The care team will determine whether a patient has capacity to make the decision whether to participate or not. If determined to be suitable for the study, the patient will complete a written informed consent sheet. There will be an aphasia friendly version of the information sheet and consent form. Confidentiality Participants will be assured of the confidentiality of the research process. All data will be anonymised using alpha-numeric code which will be stored on a password protected network, accessible by only the named researchers involved in the study. Any hard copies of data will be kept in a locked filing cabinet at the University of Winchester (King Alfred campus, Centre for Sport). The only people with access to this filing cabinet will be the named researchers. Due to collaboration between members of the University of Winchester and staff at both stroke units, data will be uploaded to a secure password protected folder on Microsoft OneDrive. Again, only the named researchers will have access to this. When the results of the study are published, all data will be presented as group means and standard deviations. The minimum amount of person-identifiable data will be collected as possible, and current UK General Data Protection Regulation (GDPR; Regulation (EU) 2016/679 of the European Parliament and of the Council of 27th April 2016) rules will be followed. All members of the research team will have completed GCP (Good Clinical Practice) training prior to the study starting. Risks/burdens Participants will be asked to complete several functional assessments at the following timepoints - baseline, every 2 weeks whilst in inpatient care up to 6 weeks, and a follow up 3-months post stroke onset. These tests will be the Timed Up and Go test (TUG), Functional Ambulation Category (FAC) and 2-minute walk test (2MWT). The TUG and FAC assessments are routinely conducted at both hospitals as part of the care. However, if these have not been conducted at each timepoint, then these two tests may have to be conducted in addition to their usual care. The 2MWT is not routinely conducted, and therefore will take up just over 2 minutes of the patient's time (due to time spent explaining and preparing for the test). To minimise risks, the care team at the stroke unit will be present and confirm that the patient can safely complete these tests while they are in inpatient care (otherwise the tests will not be conducted). Therefore, the burden of these additional assessments is that this will take up some of the patient's time. However, these are all quick tests, and will only take around 10 minutes to complete all 3 assessments. Additionally, participants will be asked to wear an ActivPAL accelerometer for 3 days at a time, at the same timepoints as for the functional assessments (baseline, every 2 weeks whilst in inpatient care for first 6 weeks, and a follow up 3-months post stroke onset). This is a small and unobtrusive device but could be seen as a burden by the participant, as they will need to wear it on their thigh for an extended period. Patients will be told about this requirement of participation before they decide whether to participate in the study or not. To minimise irritation/discomfort to the participant, the research team member who fits the device will ask the patient whether it is comfortable and readjust if not. As well as the participant, ward staff will be shown how to adjust the device, so it is more comfortable. In addition, they will be shown how to take off the device should the participant want it removed, or if there were any concerns. Finally, participants will also have Pulse Wave Analysis (PWA) and Pulse Wave Velocity (PWV) assessments conducted at each timepoint. This is a non-invasive and safe test, but the participant will need to be lying down for 20 minutes. The time burden of these assessments will also be explained and included on the information sheet so that the potential participants understand the requirements of participation. Numerous cuffs will be placed on the patient's body and attached to the Vicorder device for this time, which allows for central and peripheral blood pressure to be measured in a non-invasive way, as well as measures of arterial stiffness. A member of the research team who has experience using this device as well as the appropriate NHS honorary contract will be conducting these tests. If the patient has been discharged, the follow-up tests will be conducted at the patients' home, 3-months post stroke onset. The patient will confirm that they are comfortable and able to complete any tests before they are completed at the home. A risk assessment will be undertaken before each assessment, and any trip hazards will be removed (or change where the test takes place if object is immoveable). A member of the research team will walk behind the patient during the assessments in case support is needed. If the participant has not been discharged by this point, then the tests will be conducted at the stroke unit with a member of the care team present. Additionally, it will be made clear to participants that if they do not feel up to completing an additional test at any timepoint they will not be negatively affected in any way. Study protocol After a patient has provided informed written consent, they will be enrolled onto the study. The consent form will include consent to obtain data from medical records. The patient's height; weight; age; sex; stroke severity and type; National Institute of Health Stroke Scale; date of stroke onset and blood pressure will be recorded. Once demographic data has been recorded, baseline assessments (prior to RAGT use if recruited from Royal Bournemouth Hospital) will be conducted. These tests will include: pulse wave velocity and pulse wave analysis (via the Vicorder device); collection of accelerometer data (through wearing the ActivPAL for a period of 3 days); and completion of functional assessments (FAC, TUG, 2MWT). To collect pulse wave velocity and pulse wave analysis data, participants will be required to lie down for 30 minutes. Several cuffs will be places on the ankle, thigh, arm and neck of the participant, which are attached to the Vicorder device. These inflate and so the participant will feel a small amount of pressure. This will be conducted by a member of the research team who has experience conduction this test and hold an NHS honorary contract. For the accelerometer data collection, the ActivPAL will be attached to the participants thigh for 3 days. It is a small accelerometer device, and can be removed before the 3 day period has finished should the participant wish to end this assessment early. This will be placed and taken off by a member of the research team, who will have an NHS honorary contract. The care team will be shown how to remove the device in case the patient wants to stop the data collection and a member of the research team is not present. The first functional assessment is the FAC. This is an observational assessment of the patients movement level and will be carried out by a member of the care team, as per routine care. The TUG test will be conducted by a member of the research team, once a member of the care team has confirmed that it is safe for the participant to complete the test. This test requires a participant to stand up from a chair, walk 3 metres, turn around, walk back to the chair and sit down. The 2MWT is a test of how far the participant can walk in 2 minutes. Again, a member of the research team will conduct the test once a member of the care team has confirmed that it is safe at the time of assessment for the participant to complete this test. Patients will continue their normal care; with details of the therapy sessions (conventional physiotherapy and RAGT) being documented by the medical team. The date, time, length of session, and, if an RAGT session, the number of steps completed will be recorded. This will be recorded on a physical sheet kept at the hospital, and later transferred to a password-protected Microsoft OneDrive folder once data has been anonymised through coding. Every 2 weeks the participant is in inpatient care up to a maximum of 6 weeks, they will have the set of the assessments repeated. The final data collection session will happen at 3-months post stroke onset, which marks the end of the early subacute stroke stage. This will be conducted at the home of the participant for most people, following discharge from the stroke unit. However, if they are still at the stroke unit, the final assessment will be conducted there. The data from the two sets of participants (those exposed to RAGT and those who were not) will be compared and analysed. Once the patient's involvement in the study has ended, they will receive a personalised report (assuming they have provided consent to be contacted at a later date by a member of the research team). This will include details on their personal accelerometer/physical activity levels, functional assessment results and cardiovascular health results. Once the study has concluded, and data has been analysed, a report of the overall study findings will be sent to each participant (assuming they have provided consent to be contacted at a later date by a member of the research team).
Phase
N/ASpan
35 weeksSponsor
University of WinchesterWinchester
Recruiting
Clinical and Immunogenetic Characterization of Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR)
Giant cell arteritis (GCA), also known as temporal arteritis, is the most common form of primary systemic vasculitis, with up to 75,000 cases a year identified in the EU and US. It occurs almost exclusively in people over the age of 50 years and is considered to be a medical emergency. If not treated with high-dose glucocorticoids immediately, the thickening of the inflamed blood vessel wall can cause irreversible visual loss or stroke. GCA can lead to significant morbidity across a variety of systems, due to both the disease, and complications of treatment. Diagnosis may be confirmed with a temporal artery biopsy, imaging (e.g. USS/CT/MRA/PET-CR) or based on clinical signs (e.g. erythrocyte sedimentation rate) and symptoms (e.g. a new headache, jaw claudication, visual disturbances, temporal artery abnormality such as tenderness or decreased pulsation) . Polymyalgia rheumatica (PMR) is characterised by inflammatory limb-girdle pain with early morning stiffness, and a systemic inflammatory response demonstrated by elevated inflammatory markers. The UK GCA Consortium is a multi-centre observational study, the main arms of which recruit prospective (participants with suspected GCA) and retrospective cohorts (participants with confirmed GCA diagnosis). Analysis of data collected on these cohorts will help achieve the primary aim of finding genetic determinants of GCA and PMR susceptibility, in order to yield novel insights into disease pathogenesis. Secondary aims, and their associated analyses, are as follows: - Phenotype: characterising GCA and PMR subtypes, based on clinical features; imaging; cells; subcellular fractions and molecules in the circulation and/or arterial tissue; genetic/epigenetic/transcriptomic/proteomic or metabolomics factors, including next generation sequencing (whole exome sequencing) of selected cases. - Life impact: determining what aspects of the disease and treatments affect patients' quality of life, as assessed by patient-reported outcomes. - Long-term outcomes: characterising prognosis of GCA and PMR - both effects of the disease and its treatment - by longitudinal follow-up through electronic linkage to health records. - Exploratory analyses: exploring the potential role of environmental factors and co-morbidities on phenotype and outcomes. - Diagnosis, prognosis: improving diagnosis of GCA and PMR, and identifying factors that predict diagnosis, such as diagnostic clinical features, and prognostic and diagnostic biomarkers. - Disease activity: monitoring participants who commence a synthetic or biological disease-modifying anti-rheumatic drug (s/bDMARD). Finding a biomarker for GCA and PMR disease activity, which might be clinically useful in helping to optimise steroid and s/bDMARD treatments for individual patients.
Phase
N/ASpan
1190 weeksSponsor
University of LeedsWinchester
Recruiting
Tracking Mutations in Cell Free Tumour DNA to Predict Relapse in Early Colorectal Cancer
TRACC Part B: Despite potentially curative surgery +/- adjuvant chemotherapy, a proportional of patients with early stage CRC will experience disease relapse. Current tools for surveillance, e.g., blood sampling for tumour markers (CEA) are neither sensitive nor specific. We hypothesise that detection of mutations in circulating free DNA (cfDNA) in plasma can predict relapse in patients with early stage CRC. Circulating cell free tumour DNA (ctDNA) maintains the same mutations that are present in tumour. In colorectal cancer CRC, primary tumours and& metastases exhibit high genomic concordance. Therefore the TRACC study TRACC Part B is investigating whether serial blood samples taken from in patients with stage II and III fully resected early stage CRC colorectal cancer that have undergone potentially curative surgery, blood samples to can be used to detect and& quantify ctDNA may in order to identify minimal residual disease MRD and predict relapse earlier than existing methods. CtDNA may ultimately help identify a subset of patients that are or are unlikely to benefit from adjuvant chemotherapy and could therefore safely spare some patients from receiving unnecessary chemotherapy & its associated side-effects. TRACC Part C: We hypothesis that ctDNA guided adjuvant chemotherapy administration will enable biomarker driven selection of patients who would and would not benefit from adjuvant chemotherapy and thereby reduce the proportion of patient receiving unnecessary adjuvant chemotherapy, reducing the potential side effects associated with it, but without compromising disease free survival (DFS). : This part of the study will use tThe blood test ctDNA result from a post-operative blood sample willto guide adjuvant chemotherapy treatment decisions. The study aims to demonstrate that athe de -escalation strategy of ctDNA guided adjuvant chemotherapy is non-inferior to standard of care treatment as measured by 3 year DFS in patients with high risk stage II and stage III CRC, in those who have no evidence of MRD (ctDNA negative). after surgery for patients with colorectal cancer who are following the standard of care pathway. Patients are randomised at the post- operative time point to: Arm A (standard of care adjuvant chemotherapy), or Arm B (ctDNA guided adjuvant chemotherapy) arm. For the ct DNA guided arm, patients who are ctDNA negative at this time point will have their chemotherapy de-escalated.
Phase
N/ASpan
765 weeksSponsor
Royal Marsden NHS Foundation TrustWinchester
Recruiting
Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia
Phase
2/3Span
530 weeksSponsor
University College, LondonWinchester
Recruiting
Reliability and Validity of the Vicorder Device When Measuring Pulse Wave Velocity Within Chronic Stroke Patients
Twenty stroke patients will be recruited for this study. Participants will take part in four seperate assessments (2 hours each) with a minimum of 24 hour recovery between each session. Before each assessment participants will undertake an overnight fast (only water is allowed to be consumed prior to the assessment). If required, participants will take their medication the morning of each assessment and this will be noted.During the first session participants will be randomised into either a supine or seated condition. Participants will rest in this posture for 15 minutes. Triplicate measures of peripheral blood pressure and pulse wave analysis will be measured using the SphygmoCor XCEL and Vicorder device. A 3-lead ECG will be placed on the participant and ultrasound measures will be taken at the carotid, brachial, femoral and posterior tibial artery. This will examine the caroid-femoral pulse wave velocity (cfPWV), brachial-femoral pulse wave velocity (bfPWV), brachial-ankle pulse wave velocity (baPWV) and femoral-ankle pulse wave velocity (faPWV). Following this, the Vicorder device will be used to measure these segments. All measures will be on both symptomatic and asymptomatic sides. This procedure will be repeated in a seperate session whereby individuals will be in the other posture. Session 3 and 4 will include participants resting for 15 minutes in a supine position. Triplicate measures of peripheral blood pressure and pulse wave analysis will be taken with the Vicorder. Followed by triplicate measures of cfPWV, bfPWV, baPWV and faPWV. This will be repeated in a seated position within the same session.
Phase
N/ASpan
226 weeksSponsor
University of WinchesterWinchester
Recruiting
Reconstruction in Extended MArgin Cancer Surgery
This is an observational multicentre retrospective and prospective cohort study, and a qualitative study. The project will have three working packages: - Work package 1 - maintenance of a colorectal surgery database - Work package 2 - prospective collaborative national UK study - Work package 3 - qualitative analysis with semi-structured interviews WORK PACKAGE 1 - COLORECTAL SURGERY DATABASE: Data collected includes: - Basic demographic information - Co-morbidities at time of surgery - Other cancer treatments - Final cancer staging and diagnosis - Type of procedure - Methods of reconstruction - Use of healthcare resource: (theatre time, surgical teams, use of consumables, index operation intensive care stay, total length of stay, planned or emergency readmissions, use of imaging for complications, re-interventions, and outpatient clinic use). - Morbidity - empty pelvis syndrome complications with collation of all complications that occurred summarised into: (the highest Clavien-Dindo (CD) score, and the comprehensive complication index by accumulating CD graded complications that a patient has as a result of their surgery. - Survival: overall and disease-free survival - Patient reported outcome measures Any other routinely collected clinical data will be included. Of particular mention we will include and analyse Cardiopulmonary exercise testing data, data derived from the perioperative medicine screening and assessment, data derived from prehabilitation, radiomic data e.g. muscle/fat structure and function derived from CT, MRI or PET-CT. WORK PACKAGE 2 - PROSPECTIVE COLLABORATIVE STUDY: Abdominoperineal excision and pelvic exenteration can be used in a wide range of cancer types, and in the case of pelvic exenteration can be used to manage both recurrent and primary cancers. The principal PROM used will be the EORTC QLQ-C30 with its modular questionnaires giving additional insight into disease-specific quality of life. All amendments have been made in line with NIHR RfPB funding received in November 2024. Patients will be recruited once a decision to undertake abdominoperineal excision or pelvic exenteration surgery has taken place. Participants will be sent a participant information sheet which will include the dates of when participants can expect follow up telephone calls, with information on how to contact the study team to change these should participants wish to. Once consented participants will undergo the following PROMs as part of their baseline questionnaire: - EORTC QLQ-C30 with specific cancer-type modules - EQ-5D-5L - LRRC QoL - Decision Regret - Comprehensive Score for Financial Toxicity (COST), financial status questionnaire (non-validated) and Patient employment status questionnaires. The investigators anticipate that participants will be able to self-assess the above PROMs on a paper printed form, however a member of the research team will be available to support the participant if required. Clinical information will also be collected pre-operatively, including: demographic information, co-morbidities, cancer staging, and previous cancer treatments. Patients will be given copies of the follow up questionnaires at this time so participants have them as a reference when completing follow up questionnaires. Patients can opt for either email or telephone follow up for quality of life, if opting for email REDCap study will automatically send out emails based on the date of surgery. The patient will then undergo their surgery with method of reconstruction at the discretion of the operating surgeon(s). Following the index admission researchers will enter details on the hospital stay: - Type of procedure - Methods of reconstruction - Theatre time - Theatre teams - Use of consumables - Length of intensive care and hospital stay - Use of imaging for complications - Re-interventions for complications - Discharge destination following index admission - Final cancer staging and other pathological outcomes. - Perineal and empty pelvis morbidity, and overall Clavien-Dindo and Comprehensive Complication Index - NHS healthcare utilisation costs - If applicable survival and cause of death At 3 months post-operatively questionnaires will be repeated over the telephone including: - EORTC QLQ-C30 with cancer-specific module - EQ-5D-5L - LRRC QoL - Decision Regret - Comprehensive Score for Financial Toxicity (COST), Patient reported heath resource utilisation and NHS healthcare utilisation costs. At this same time point researchers will review routinely collected clinical data and use of in-hospital health resources to include: - In-hospital health resource use: planned or emergency re-admissions, use of imaging to investigate complications, re-interventions (surgical and radiological), planned or unplanned outpatient visits. - Longitudinal CCI scores updated, and if applicable an increase in CD if a more severe complication develops. - If applicable cancer recurrence, survival and cause of death will be recorded. Patients will be emailed or telephoned on the date specified on their participant information sheet, however if this time is not convenient then a better time will be arranged with the patient. If participants do not respond to the email or first telephone call then the investigators will make a further three separate attempts to contact the patient. If there is still no response participants will be deemed lost to the study. This follow up process will be repeated again at 6 months and 12 months. At the 12 month time point the investigators will ask patients additional questions on their use of health care resources and their current financial status, to include: - Use of community health resource use due to complications including: GP appointments and nursing home care days required for recovery from surgery. - Use of healthcare resources at hospitals other than the treating hospital - clinic appointments and admissions At the end of this time the patient will have completed the study. WORK PACKAGE 3 - QUALITATIVE STUDY: The qualitative study will recruit patients from work packages 1 and 2. The investigators will invite 30 purposefully sampled patients that are 3 months following their surgery. Suitable patients will be contacted with a posted participant information sheet and a telephone follow up call to allow participants to ask questions about the study. Following informed consent semi-structured interviews will take place with semi-structured open questions to guide the discussions. Interviews will be recorded on an encrypted audiorecorder and then transcribed. The investigators will initially undertake three pilot interviews to review that the semi-structured interview schedule is adequate to fully explore our objectives and to obtain good quality interview transcripts for analysis. These pilot interviews once completed will be reviewed by the research team. The semi-structured interview schedule questions may be changed if the interviews are of poor quality, pilot interviews demonstrate new insights from participants that suggest fruitful lines of enquiry, or inconsistencies that require further exploration. If subsequent interviews are very different than the pilot interviews following these changes, then these early interviews will not be included in the qualitative analysis and additional patients will be recruited. Patients recruited at 3-months following surgery will be offered a repeat interview at 12-months following their surgery DATA ANALYSIS PLAN: Statistical analysis: The investigators will be collecting data on the timepoints as described above. Continuous data will be will be summarised using descriptive statistics (mean, median, standard deviation, lower and upper quartiles). Categorical data will be summarised using counts and percentages. As studies are non-randomised, the investigators will utilise regression models and principal component analysis to adjust for confounding in this observational study. In order to obtain our outcomes a brief summary of analyses is below. Work package 1 (Colorectal Database): Primary analysis: - Frequency of morbidity relating to the empty pelvis syndrome and perineal wound will be compared for different types of perineal reconstruction will be analysed using multiple linear regression. Secondary analysis: - Overall morbidity will be obtained using highest CD scores for different methods of perineal reconstruction analysed using multiple linear regression. - Disease free and overall survival will be analysed using Kaplan-Meier curves and log rank tests with a multivariate Cox regression hazard model to identify factors independently associated with survival, including method of reconstruction. Exploratory analysis: - Other factors including age, gender, BMI, final staging, co-morbidities, type of operation, neoadjuvant chemoradiotherapy and use of intra-operative electron radiotherapy will be included in the analysis - Other outcomes including primary operation time, lengths of stay, and readmissions will be explored Work package 2 (prospective study): Primary and secondary analysis: - Patient reported outcome measures will be analysed using regression models, including linear mixed-effects models for repeat measures and adjusted analyses. - The same clinical data fields will be collected as per work package 1, the analysis above repeated with exploratory analysis to find factors that are independently significantly associated with changes in the PROMs. Health economic analysis: Work package 1 (retrospective study): The investigators will collect data on use of hospital healthcare resources in each patient group. The investigators will collect resource use for each parameter required for each patient. The investigators will then undertake costing using a micro-costing approach and health resource group costing for each parameter. Applying costs to each parameter will use a combination of manufacturer prices for consumables, National Cost Collection for the NHS, National Schedule of NHS Costs, NHS National Tariff and the Unit Costs of Health and Social Care from the Personal Social Services Research Unit. The investigators will then report overall costs associated with different methods of perineal reconstruction and the cost of complications that were encountered. Work package 2 (prospective study): The investigators will collect hospital healthcare resource use data prospectively and apply micro-costing to these parameters in the same way as per work package 1 for each patient and their method of reconstruction. The investigators will also ask patients to provide us with use of community healthcare resources as a result of their surgery, data for which the investigators will not be able to obtain from their clinical notes. Participants will receive EQ-5D-5L and EORTC QLQ-C30 questionnaires at baseline, 3 months, 6 months and 12 months. From these responses the investigators will map onto EQ-5D-3L in order to reduce the overall number of questionnaires patients are undertaking in our study. This will allow us to plot EQ-5D-3L responses for different methods of reconstruction and plot the area under the curve. Within the trial time a health economic model would be built which would follow the NICE reference case and ISPOR Task Force guidelines on health economic analysis. This will enable us to present Quality Adjusted Life Years and incremental cost-effective ratios for the different methods of perineal reconstruction. Qualitative analysis: Audio transcription will be transcribed verbatim, checked against the recording and anonymised. Data will be uploaded to NVivo for data management. Preliminary summaries will be written after each interview to identify emerging themes to follow-up discussions. The follow-up interview will ask patients to reflect on the content of their previous interview and discuss any changes. Longitudinal interview analyses will use constant comparative methods from grounded theory and data coded using NVivo's framework matrix facility to examine themes longitudinally, enabling comparisons within each case and across cases, focusing on changes over time. The stages of data analysis, drawing on longitudinal comparisons, will include: 1. Initial reading: Review interview data. 2. Preliminary coding: Two researchers code the data. 3. Team meeting: Discuss and refine codes with wider research/PPI team. 4. Individual Case Coding: Code all interview data for each participant. 5. Categorising Codes: Group codes into categories for each case. 6. Longitudinal comparisons: Within case and category comparisons focussing on changes over time. 7. Focused coding: Examine categories in relation to emerging concepts and phases. 8. Discussion on Themes: PPI co-led focus group discussions of final themes. 9. Development and Dissemination: Report write up are dissemination. Based on an iterative process, emerging themes will be used to develop explanatory accounts. Analysis will draw on sociological perspectives of illness adaptation, recovery and self-management in addition to psychological theories of individual behaviour change. All qualitative and quantitative data will inform 3 patient focus groups, where PPI and charity collaborators along with 5 newly trained PPI members will discuss data analyses from a patient perspective, contributing to initial discussions around developing a patient decision aid.
Phase
N/ASpan
294 weeksSponsor
University Hospital Southampton NHS Foundation TrustWinchester
Recruiting
Repurposed Drugs to Improve Haematological Responses in Myelodysplastic Syndromes
Phase
2Span
184 weeksSponsor
Prof. Janet DunnWinchester, Hampshire
Recruiting
Effect of a Community Exercise Programme on Stroke Patients
Design: The present study will be a controlled trial without randomisation. This is considered appropriate by the research team given the potential for participants of the exercise group to experience improved health outcomes compared with those assigned to a control group (receiving usual clinical care, who elect not to attend exercise classes). Accordingly, all individuals diagnosed with stroke from Hampshire Hospitals NHS Foundation Trust, who meet inclusion criteria (i.e. eligible to engage in a stroke rehabilitation programme) will be presented with an equal opportunity to attend low-cost, community-based exercise classes. Health-related quality of life, with researchers considering participation against various measures of physical and psycho-social health outcomes will be assessed at baseline, post-intervention (following possible engagement in 12 weeks of exercise classes) and at 6-month follow-up. Attendance to exercise classes will be optional but will be monitored to assess exercise adherence. Participants electing not to attend exercise classes will form a control group, providing evidence of the usual care pathway, and will also be asked to attend the post-intervention and 6-month follow-up assessment. Exercise classes will be provided through the Health Enhancing Lifestyle Programme (HELP) Hampshire Stoke Clinic. The HELP clinic is a community-based initiative that signposts and provides individuals who have experienced stroke and/or TIA to various accessible and affordable exercise and educational opportunities and is led by the University of Winchester in collaboration with the Hampshire Hospitals NHS Foundation Trust (HHFT) and Hobbs Rehabilitation, a specialist, independent, neuro-physiotherapy provider. As the HELP Hampshire Stroke Clinic provides a service to the stroke community alongside the usual care pathway, some individuals referred to the clinic may choose to participate in the exercise classes but not to participate in the study. This is a fundamental right of the individual. Such individuals will not be disadvantaged in anyway as it will not impact the opportunity for them to access the exercise classes, nor will it affect the nature of the exercises or any other part of the service provided by the HELP Hampshire Stoke Clinic. The research team have discussed the design of the present study with the clinical team at HHFT, including stoke consultants, occupational therapists and physiotherapists, and neuro-physiotherapists from Hobbs Rehabilitation. The study has also been discussed at a Patient and Public Involvement (PPI) meeting, and with people who are currently engaging in the HELP Hampshire Stroke Clinic. The project has been discussed with Prof Maria Stokes and Dr Danielle Lambrick from the School of Health Sciences at the University of Southampton. Recruitment: Potential participants will initially be identified by the healthcare team at Hampshire Hospitals NHS Trust(i.e. stroke consultants, occupational therapists, physiotherapists), according to study inclusion/exclusion criteria. The clinical team will gain written consent from potential participants for their contact details to be provided to the research team at the University of Winchester (Dr James Faulkner) who will then contact patients directly to discuss their potential participation. As described above (Design), the research team will make every effort to provide all participants a fair and equal opportunity to participate in all available exercise classes so as to avoid the introduction of any bias relating to potential demographic or socioeconomic differences. Informed Consent: Participants will be provided with a study information sheet which outlines their possible involvement and will have opportunities to discuss the study with the research team prior to making a decision as to whether to participate or not. Each patient will have had sufficient time (>24-hours) to read the information sheet and discuss their options with significant others, and will be able to ask questions to the research team both by phone prior to attending their first assessment visit and upon arrival to the Physiology Laboratory at the University of Winchester before providing voluntary written consent for participation in this study. Participants will be reminded that attendance to each assessment visit is compulsory but that attendance to any of the exercise classes is optional and that they can withdraw from the study at any time and without repercussion of any kind. The research team have met with Speech and Language therapists at HHFT to discuss potential issues concerning consent in patients with aphasia. Patients who are not able to fully comprehend the nature of the study and involvement in the HELP Hampshire Stroke Clinic will be excluded from participation. Risks, burdens and benefits: Participants may experience mild discomfort while providing a fingertip blood sample and during analysis of blood pressure (measured at the upper-left arm) during the baseline, post-intervention and 6-month follow-up assessment. Participants will be fully briefed about both tests and will have likely experienced both procedures during usual clinical care. Baseline and 12- and 36 week follow-up assessments Participants will complete an online baseline assessment whereby they will complete a general health history questionnaire and a series of quality of life, physical activity and psycho-social questionnaires (see outcome measures for further information). Participant demographics (height, weight) will be recorded, while participants will also complete a sit-to-stand test (see outcome measures for further information). All measures will be repeated at the 12 and 36 week follow-up assessment. On completion of the baseline assessment, participants will be able to attend the exercise classes. Exercise classes During the exercise classes, individuals will be required to exercise in bouts of intensities up to their self-selected maximum which may result in discomfort including fatigue and nausea. To minimise this risk, periods of rest will be scheduled, and plain water will be available ad libitum during all functional trials and exercise classes. Researchers who are first aid trained will be in attendance for all sessions and will have access to an automated external defibrillator and mobile phone for emergency use. As part of the study, participants will be invited to attend low-cost, community-based exercise clinics led by specialist Physiotherapists, and will continue to have access to these classes after their participation in the research study has ended. Exercise classes will be delivered in person (face-to-face) or online. All exercise classes will last 60 minutes, with a minimum of one face-to-face and one online exercise class available to participants each week. Both face-to-face and online exercise classes will include a range of seated and standing resistance and aerobic exercises (e.g., sit-to-stand, step-ups, bicep curls, walking). Costs: Although the HELP Hampshire Stroke Clinic is a not-profit project, attendees pay £5 per exercise class to allow us to cover the costs of practitioner hire and venue hire. Participants incur no costs for the baseline, post-intervention and 6-month follow-up assessments.
Phase
N/ASpan
107 weeksSponsor
University of WinchesterWinchester
Recruiting